TCD with Transfusions Changing to Hydroxyurea - SDMC

描述(由申请人提供)： 中风发生在5-10%的SCA儿童中，是一种破坏性的临床事件，会导致严重的运动和神经认知障碍。为了帮助预防最初的(原发)卒中，患有SCA的年轻患者可以定期接受TCD筛查，以确定脑血管中动脉血流速度升高的儿童，这预示着原发卒中风险的增加。对于大脑中动脉(MCA)或颈内动脉(ICA)的时间平均最大血流速度(TAMV)升高到“异常”范围(=200厘米/秒)的儿童，慢性红细胞输注显著降低了原发性中风的风险。在这种情况下，输血可以预防首次中风，但有严重的副作用限制了其长期用途。输血传播感染源，导致红细胞同种异体抗体或自身抗体的形成，并导致铁超载。输血获得性铁超载被认为是接受输血预防原发性卒中的年轻SCA患者的发病率和死亡率的来源。螯合疗法可以帮助防止铁蓄积，但难以耐受，不遵守规定的情况很常见。显然需要一种替代输血预防的初级卒中预防方法，特别是提供一个机会来解决输血后天获得性铁超载的问题。我们提出了一项针对镰状细胞性贫血(SCA)和经颅多普勒(TCD)血流速度异常的儿童的第三阶段随机临床试验，称为TCD换血为羟基尿素(Twitch)试验。我们的假设是，羟基尿素可以保持与红细胞输注相似的TCD速度，因此对于SCA高危儿童的一级卒中预防来说，它是一种非劣势疗法。Twitch试验的主要目的是比较标准疗法(输液)和替代疗法(羟基尿素)对慢性输液异常TCD速度的SCA儿童维持TCD速度的作用。Twitch的其他目标包括比较原发中风发病率的标准和替代疗法，确定非中风神经事件和其他镰状细胞相关事件的频率，管理铁超载，评估生长和发育，记录不良事件，以及生活质量的测量。(摘要结束)

DESCRIPTION (provided by applicant): Stroke occurs in 5-10% of children with SCA, and is a devastating clinical event that results in severe motor and neurocognitive deficits. To help prevent an initial (primary) stroke, young patients with SCA can receive periodic TCD screening to identify children with elevated arterial velocities in the cerebral vasculature, which portends increased primary stroke risk. For children with time-averaged maximum velocities (TAMV) in the middle cerebral artery (MCA) or internal carotid artery (ICA) elevated to the "abnormal" range (=200cm/sec), chronic erythrocyte transfusions significantly lower the risk of primary stroke. In this setting, transfusions can prevent first stroke but have serious side-effects limiting their long-term utility. Transfusions transmit infectious agents, lead to erythrocyte alloantibody or autoantibody formation, and result in iron overload. Transfusion acquired iron overload is recognized as a source of morbidity and mortality for young patients with SCA receiving transfusions for prevention of primary stroke. Chelation therapy can help prevent iron accumulation, but is difficult to tolerate and non-compliance is common. An alternative to transfusion prophylaxis for primary stroke prevention is clearly needed, especially one that also provides an opportunity to address the issue of transfusion acquired iron overload. We propose a Phase III randomized clinical trial for children with sickle cell anemia (SCA) and abnormal Transcranial Doppler (TCD) velocities, termed the "TCD With Transfusions Changing to Hydroxyurea" (TWiTCH) trial. Our hypothesis is that hydroxyurea can maintain a similar TCD velocity as erythrocyte transfusions, and therefore serve as non-inferior therapy, for primary stroke prevention in high risk children with SCA. The primary aim of the TWiTCH trial is to compare standard therapy (transfusions) to alternative therapy (hydroxyurea) for maintenance of TCD velocities in children with SCA on chronic transfusions for abnormal TCD velocities. Additional aims of TWiTCH include comparison of standard to alternative therapy for incidence of primary stroke, determination of the frequency of non-stroke neurological events and other sickle cell-related events, management of iron overload, assessment of growth and development, recording of adverse events, and measurement of quality of life. (End of Abstract)